The consideration of surgery on primary lesion of advanced non-small cell lung cancer.

BACKGROUND: Numerous reports have shown that medical treatment confers excellent survival benefits to patients with advanced stage IV non-small cell lung cancer (NSCLC). However, the implications of surgery for primary lesions as palliative treatment remain inconclusive. METHODS: We retrospectively extracted clinical data from the Surveillance, Epidemiology, and End Results Program (SEER) database and selected patients with stage IV NSCLC. Patients were classified into non-surgery and surgery groups, and propensity score matching (PSM) analysis was performed to balance the baseline information. Patients in the surgery group, whose overall survival (OS) was longer than the median survival time of those in the non-surgery group, were deemed to benefit from surgery. We evaluated the efficacy of three surgical techniques, namely, local destruction, sub-lobectomy, and lobectomy, on the primary site in the beneficial population. RESULTS: The results of Cox regression analyses revealed that surgery was an independent risk factor for both OS (hazard ratio [HR]: 0.441; confidence interval [CI]: 0.426-0.456; P < 0.001) and cancer-specific survival (CSS) (HR: 0397; CI: 0.380-0.414; P < 0.001). Notably, patients who underwent surgery had a better prognosis than those who did not (OS: P < 0.001; CSS: P < 0.001). Moreover, local destruction and sub-lobectomy significantly compromised survival compared to lobectomy in the beneficial group (P < 0.001). After PSM, patients with stage IV disease who underwent lobectomy needed routine mediastinal lymph node clearing (OS: P = 0.0038; CSS: P = 0.039). CONCLUSION: Based on these findings, we recommend that patients with stage IV NSCLC undergo palliative surgery for the primary site and that lobectomy plus lymph node resection should be conventionally performed on those who can tolerate the surgery.

The Implication of Liquid Biopsy in the Non-small Cell Lung Cancer: Potential and Expectation.

Nowadays, lung cancer has remained the most lethal cancer, despite great advances in diagnosis and treatment. However, a large proportion of patients were diagnosed with locally advanced or metastatic disease and have poor prognosis. Immunotherapy and targeted drugs have greatly improved the survival and prognosis of patients with advanced lung cancer. However, how to identify the optimal patients to accept those therapies and how to monitor therapeutic efficacy are still in dispute. In the past few decades, tissue biopsy, including percutaneous fine needle biopsy and surgical excision, has still been the gold standard for examining the gene mutation such as EGFR, ALK, ROS, and PD-1/PD/L1, which can indicate the follow-up treatment. Nevertheless, the biopsy techniques mentioned above were invasive and unrepeatable, which were not suitable for advanced patients. Liquid biopsy, accounting for heterogeneity compared with tissue biopsy, is an alternative technique for monitoring the mutation, and a large quantity of research has demonstrated its feasibility to detect the circulating tumor cell, cell-free DNA, circulating tumor DNA, and extracellular vesicles from peripheral venous blood. The proposal of the concept of precision medicine brings a novel medical model developed with the rapid progress of genome sequencing technology and the cross-application of bioinformation, which was based on personalized medicine. The emerging method of liquid biopsy might contribute to promoting the development of precision medicine. In this review, we intend to describe the liquid biopsy in non-small cell lung cancer in detail in the aspect of screening, diagnosis, monitoring, treatment, and drug resistance.

Mucosa­associated lymphoid tissue in the central nervous system presenting as meningioma: A case report.

Mucosa-associated lymphoid tissue (MALT) lymphoma involving meningeal tissue is rare condition, easily mistaken for meningiomas upon imaging. In this report, a case of primary left temporal lobe MALT lymphoma that was initially misdiagnosed as temporal meningioma is presented, with subsequent investigation into the mechanism and treatments. Clinically, MALT lymphomas can be easily confused with meningiomas based solely on imaging and clinical manifestations. MALT lymphomas are indolent, localized lesions that can be cured through surgical resection and radiotherapy. Currently, radiotherapy is the most commonly used treatment; however, the patient in the present report did not receive any chemotherapy or radiotherapy after surgery, and recent related examinations revealed a recurrence of lymphomas that had metastasized throughout the body. As a result, future patients may benefit from chemotherapy or radiotherapy, and clinicians should be more meticulous regarding patient follow-up.

Tracheal tunica adventitia invasion after lobectomy in patients with non-small cell lung cancer.

BACKGROUND: For patients with non-small cell lung cancer, a negative margin status is required for radical pulmonary surgery. Residual disease of the margin has been thoroughly studied in the past few decades. However, the prognostic significance of tracheal tunica adventitia invasion after lobectomy remains unclear. In this study, we aimed to investigate the clinical influence of tracheal tunica adventitia invasion after lobectomy. METHODS: We retrospectively collected the clinical data of 591 patients who consecutively underwent pulmonary lobectomy, including sleeve lobectomy, between 2012 and 2018 at Shanghai Chest Hospital. According to the tracheal tunica adventitia invasion status, we allocated the patients into 2 groups (tracheal tunica adventitia invasion and non-tracheal tunica adventitia). Disease-free and overall survival were evaluated, and we discussed the necessity of radiotherapy in patients with tracheal tunica adventitia. RESULTS: After propensity score matching to balance baseline characteristics, there were 167 individuals in the tracheal tunica adventitia invasion and non-tracheal tunica adventitia groups. In the hazard analysis, we found that tracheal tunica adventitia increased the risk of recurrence (hazard ratio: 0.652; P = .002) and impaired long-term survival (P < .001). Subgroup analysis revealed that tracheal tunica adventitia was an important risk factor, especially when the hilar lymph nodes were positive. In addition, tracheal tunica adventitia invasion promoted extra-thoracic lymph node metastasis. We discovered that radiotherapy did not improve the prognosis of patients in the tracheal tunica adventitia invasion group. CONCLUSIONS: After lobectomy, tracheal tunica adventitia invasion is a risk factor for non-small cell lung cancer and potentially increases extra-thoracic lymph node metastasis. Moreover, tracheal tunica adventitia invasion is not sensitive to postoperative radiotherapy.

The Importance of M1-and M2-Polarized Macrophages in Glioma and as Potential Treatment Targets.

Glioma is the most common and malignant tumor of the central nervous system. Glioblastoma (GBM) is the most aggressive glioma, with a poor prognosis and no effective treatment because of its high invasiveness, metabolic rate, and heterogeneity. The tumor microenvironment (TME) contains many tumor-associated macrophages (TAMs), which play a critical role in tumor proliferation, invasion, metastasis, and angiogenesis and indirectly promote an immunosuppressive microenvironment. TAM is divided into tumor-suppressive M1-like (classic activation of macrophages) and tumor-supportive M2-like (alternatively activated macrophages) polarized cells. TAMs exhibit an M1-like phenotype in the initial stages of tumor progression, and along with the promotion of lysing tumors and the functions of T cells and NK cells, tumor growth is suppressed, and they rapidly transform into M2-like polarized macrophages, which promote tumor progression. In this review, we discuss the mechanism by which M1- and M2-polarized macrophages promote or inhibit the growth of glioblastoma and indicate the future directions for treatment.

The location of visceral pleural invasion in stage IB patients with non-small cell lung cancer: Comparison and prognosis.

OBJECTIVES: Recently, early-stage lung cancer has been drawing more attention, especially in screening and treatment. Visceral pleural invasion in stage IB cancer is considered as risk factor for poor prognosis. Herein, we aimed to study the distinction between the different locations of visceral pleural invasion. METHODS: In this retrospective cohort study, we summarized 58,242 patient cases that underwent surgery from 2015 to 2018 at Shanghai Chest Hospital. Of those patients, 389 met the inclusion criteria. Patients with PL3 pleural invasion were excluded. The patients were dichotomized into the interlobar pleural and peripheral pleural groups. The outcomes measured were overall survival (OS) and recurrence-free survival (RFS) rates. RESULTS: According to the initial analysis, the baseline characteristics of the two groups were largely balanced. In multivariate Cox analyses, we found that the location of visceral pleural invasion was not a risk factor for prognosis in the overall population (RFS: P = 0.726, OS: P = 0.599). However, we discovered that relative to patients with peripheral pleura invasion, those with interlobar pleura invasion, PL1 invasion, lesions with greater than 3 cm solid components, and those who underwent segmentectomy had a compromised prognosis. Additionally, tumors larger than 3 cm in size with interlobar pleura invasion showed poor prognosis in patients who underwent postoperative chemotherapy. CONCLUSIONS: In most cases, the location of tumor invasion did not worsen the postoperative prognosis of stage IB non-small cell lung cancer patients with visceral pleural invasion. However, interlobar pleural invasion still had some potential risks compared to that of peripheral pleural invasion.

Analysis for discharge within 2 days after thoracoscopic anatomic lung cancer surgery.

OBJECTIVES: The risk and beneficial factors of early discharge after thoracoscopic anatomic lung cancer surgery are unknown, and this study aims to investigate predictors and associated 30-day readmission for early discharge. METHODS: We performed a single-center retrospective analysis of 10,834 consecutive patients who underwent thoracoscopic anatomic lung cancer surgery. Two groups were determined based on discharge date: "discharged by postoperative Day 2" and "discharged after postoperative Day 2." Univariable and multivariable analysis were conducted to identify predictors for discharge. Using propensity score matching (PSM) to compare 30-day readmission rate between two cohorts. RESULTS: A total of 1911 patients were discharged by postoperative Day 2. Multivariable analysis identified older age (odds ratio (OR) = 1.014, p < 0.001), male sex (OR = 1.183, p = 0.003), larger tumor size (OR = 1.248, p < 0.001), pleural adhesions (OR = 1.638, p = 0.043), lymph nodes calcification (OR = 1.443, p = 0.009), advanced clinical T stage (vs. T < 2, OR = 1.470, p = 0.010), lobectomy resection (vs. segmentectomy resection, OR = 2.145, p < 0.001) and prolonged operative time (OR = 1.011, p < 0.001) as independent risk factors for discharge after postoperative Day 2. Three adjustable variables including higher FEV1 /FVC (OR = 0.989, p = 0.001), general anesthesia (GA) plus thoracic paravertebral blockade (vs. GA alone, OR = 0.823, p = 0.006) and uni-portal thoracoscopic surgery (vs. multi-portal, OR = 0.349, p < 0.001) were associated with a decreased likelihood of discharge after postoperative Day 2. Before and after a 1:1 PSM, discharged by postoperative Day 2 did not increase the risk of 30-day readmission compared to counterparts. CONCLUSIONS: Carefully selected patients can be safely discharged within 2 days after thoracoscopic anatomic lung cancer surgery. Three modifiable variables may be favorable for promoting discharge by postoperative Day 2.

shRNA­mediated knockdown of KNTC1 inhibits non-small-cell lung cancer through regulating PSMB8.

In view of the important roles played by Kinetochore proteins in mitosis, we believed that they may contribute to the development and progression of human cancers, which has been reported recently elsewhere. Kinetochore-associated 1 (KNTC1) participates in the segregation of sister chromatids during mitosis, the effects of which on non-small-cell lung cancer (NSCLC) remain unclear. Here, we sought to identify the biological significance of KNTC1 in NSCLC. KNTC1 protein expression in NSCLC tissues was investigated by immunohistochemistry. Lentivirus delivered short hairpin RNA (shRNA) was utilized to establish KNTC1 silence NSCLC cell lines. The effects of KNTC1 depletion on NSCLC cell proliferation, migration, apoptosis, and tumor formation were analyzed by MTT assay, wound-healing assay, transwell assay, flow cytometry assay, and in nude mouse models in vivo. After KNTC1 reduction, NSCLC cell viability, proliferation, migration, and invasion were restrained. A xenograft tumor model was also provided to demonstrate the inhibited tumorigenesis in NSCLC. In addition, the downstream mechanism analysis indicated that KNTC1 depletion was positively associated with PSMB8. The findings of the present study suggested that KNTC1 may have a pivotal role in mediating NSCLC progression and may act as a novel therapeutic target for NSCLC.

The outcomes of margin status after sleeve lobectomy for patients of non-small cell lung cancer.

BACKGROUND: Sleeve lobectomy is recognized as an alternative surgical operation to pneumonectomy because it preserves the most pulmonary function and has a considerable prognosis. In this study, we aimed to investigate the implications of residual status for patients after sleeve lobectomy. METHODS: In this retrospective cohort study, we summarized 58 242 patients who underwent surgeries from 2015 to 2018 in Shanghai Chest Hospital and found 456 eligible patients meeting the criteria. The status of R2 was excluded. The outcomes were overall survival (OS) and recurrence-free survival (RFS). We performed a subgroup analysis to further our investigation. RESULTS: After the propensity score match, the baseline characteristic was balanced between two groups. The survival analysis showed no significant difference of overall survival and recurrence-free survival between R0 and R1 groups (OS: p = 0.053; RFS: p = 0.14). In the multivariate Cox analysis, we found that the margin status was not a dependent risk factor to RFS (p = 0.119) and OS (p = 0.093). In the patients of R1, N stage and age were closely related to OS, but we did not find any significant risk variable in RFS for R1 status. In the subgroup analysis, R1 status may have a worse prognosis on patients with more lymph nodes examination. On further investigation, we demonstrated no differences among the four histological types of margin status. CONCLUSION: In our study, we confirmed that the margin status after sleeve lobectomies was not the risk factor to prognosis. However, patients with more lymph nodes resection should pay attention to the margin status.

Reconstruction of the trachea and carina: Surgical reconstruction, autologous tissue transplantation, allograft transplantation, and bioengineering.

There have been significant advancements in medical techniques in the present epoch, with the emergence of some novel operative substitutes. However, the treatment of tracheal defects still faces tremendous challenges and there is, as yet, no consensus on tracheal and carinal reconstruction. In addition, surgical outcomes vary in different individuals, which results in an ambiguous future for tracheal surgery. Although transplantation was once an effective and promising method, it is limited by a shortage of donors and immune rejection. The development of bioengineering has provided an alternative for the treatment of tracheal defects, but this discipline is full of ethical controversy and hindered by limited cognition in this area. Meanwhile, progression of this technique is blocked by a deficiency in ideal materials. The trachea together with the carina is still the last unpaired organ in thoracic surgery and propososal of a favorable scheme to remove this dilemma is urgently required. In this review, four main tracheal reconstruction methods, especially surgical techniques, are evaluated, and a thorough interpretation conducted.

Short-term outcomes of robot-assisted versus thoracoscopic-assisted minimally invasive esophagectomy.

BACKGROUND: Robot-assisted (RA) and thoracoscopic-assisted (TA) minimally invasive esophagectomy (MIE) are surgical techniques for the treatment of esophageal cancer. This study aims to compare short-term outcomes of RAMIE to TAMIE. METHODS: We conducted a single-center retrospective analysis between January 2016 and December 2019, including 1012 consecutive patients who underwent MIE, 437 in the RAMIE group and 575 in the TAMIE group. A 1:1 propensity score matching (PSM) analysis was performed to compare short-term outcomes. RESULTS: The vast majority of patients had squamous cell carcinoma (972/1012, 96.0%). Radical resection (R0) was performed in 945 (93.4%) patients with a mean total number of dissected lymph nodes of 22.6±11.0. The incidence of postoperative pulmonary complications (PPCs) was 44.1% (446/1012). The median length of hospital stay was 9 days, and no 30-day mortality was observed. We evaluated short-term outcomes in 544 patients (272 pairs) treated with RAMIE or TAMIE after a 1:1 PSM. Compared with TAMIE group, patients received RAMIE had shorter operative time (291.6±60.5 vs 247.2±51.0min, P<0.001), more left recurrent laryngeal lymph node dissected (2.0±1.9 vs 2.5±2.3, P=0.007), comparable total number of lymph node dissected (22.9±11.4 vs 22.8±9.8, P=0.913) and R0 resection rate (90.8% vs 93.4%, P=0.266) and similar short-term outcomes including PPCs, surgical complications, length of ICU and hospital stays, ICU readmission rate, 30-day readmission and mortality rates (P>0.05). CONCLUSIONS: RAMIE is an alternative minimally invasive option to TAMIE, with promising oncological results especially in left RLN lymph node dissection and comparable short-term outcomes.

The significance of systematic lymph node dissection in surgery for early-stage non-small cell lung cancer patients aged ≤40 years.

BACKGROUND: Surgery remains the best option for treating early-stage non-small cell lung cancer (NSCLC), and lymph node dissection (LND) is an important step in this approach. However, the extent of LND in the general age population, especially in young patients, is controversial. This retrospective study aimed to investigate the correlation between systematic lymph node dissection (SLND) and prognosis in young (≤40 years) patients with stage IA NSCLC. METHODS: Clinicopathological data of 191 patients aged ≤40 years who underwent surgical pulmonary resection for stage IA NSCLC between January 2010 and December 2016 were retrospectively collected. Of the patients, 104 received SLND (SLND group), while the other 87 patients underwent sampling or no LND (non-SLND group). The disease-free survival (DFS) and overall survival (OS) curves of the patients from each group were plotted using the Kaplan-Meier method, and the correlations of the patients' clinical factors with prognosis were also analyzed. RESULTS: The median follow-up period was 55 months. During follow-up, 7 patients died, and recurrence or metastasis was detected in 16 patients. Kaplan-Meier analysis revealed no difference in DFS (P=0.132) between the SLND and non-SLND group, but a significant difference was found between the groups in OS (P=0.022). Additionally, there was no statistically pronounced difference in OS or DFS between male and female patients. Multivariate survival analysis showed that the type of SLND, as well as tumor size, is an independent prognostic factor for DFS (HR, 3.530; 95% CI, 1.120-11.119; P=0.031) and OS (HR, 13.076; 95% CI, 1.209-141.443; P=0.034). CONCLUSIONS: For young (age ≤40) stage IA NSCLC patients with pathological invasive adenocarcinoma, intraoperative SLND can improve the DFS and OS. Further studies are needed to verify the most optimal degree of LND in young patients.